The present invention relates to a method for stabilizing an aqueous protein solution against exogenous stress comprising the step of filing a container with said aqueous protein solution so that the container substantially lacks a gas headspace when closed.
Stabilization of aqueous protein solutions against exogenous stresses, e.g. mechanical stresses such as shaking, still represents a technical difficulty in the pharmaceutical industry. It is a known fact that aqueous protein solutions have a tendency to aggregate upon mechanical stress. Such mechanical stress almost always occurs upon transportation of the aqueous protein solution, e.g. in containers such as pharmaceutical vials.
A common solution adopted in the art is physico-chemical stabilization using, for instance, chemical stabilizers such as polysorbates such as Polysorbate 20 (also known as Tween 20™), Polysorbate 80 (Tween 80™), Poloxamer 188 and other surfactants.
However, it can be easily understood that stabilization without using chemical products would be of great advantage. In particular, the impact of chemical stabilizers on the safety of the human may be implicated. Therefore, regulatory authorities usually desire to minimize the number and quantity of chemical stabilizers included in a pharmaceutical formulation.
A lesser consideration compared to health concerns is the cost of chemical stabilizers that have to be added to stabilize an aqueous protein solution.
It hence clearly appears that there is a need for a method for stabilizing an aqueous protein solution against mechanical stress without using chemical stabilizers.
It is with this objective in mind that the Applicants found that an aqueous protein solution can surprisingly be stabilized against exogenous stress, e.g. mechanical stress, using a method comprising the step of filling a container with the aqueous protein solution so that the container substantially lacks a gas headspace when closed. Such a method does not require the use of chemical stabilizers.
This finding is even more surprising in view of the commonly established technical prejudice that has been overcome. Indeed, the method according to the invention overcomes the well known technical prejudice that chemical stabilizers must be used to stabilize an aqueous protein solution against mechanical stresses.